A gene therapy based on CRISPR activation (CRISPRa) shows promise for treating SCN2A-related disorders, which may be associated by epilepsy and other conditions and are caused by gene haploinsufficiency. This is suggested by a recent study published in Nature.

SCN2A is a gene that codes for a sodium channel essential for brain cell communication. It is one of the most common single-gene contributors to neurodevelopmental disorders associated with haploinsufficiency, including autism, intellectual disability, and epilepsy. Haploinsufficiency occurs when one of the two copies of a gene is faulty or missing, resulting in too little protein to support normal function.

The study’s authors applied CRISPRa in mice to boost the activity of the remaining, correct SCN2A gene copy. They used a harmless virus to deliver CRISPRa to the cells, targeting a promotor, a kind of natural “switch”, of the SCN2A gene. This restored normal electrophysiological function and protected the animals from seizures—even when treatment was started during adolescence. The treatment was well tolerated with no harmful overactivity in the brain. Similar benefits were also observed in human neurons derived from stem cells.